1. Academic Validation
  2. BKCa channel participates in insulin-induced lipid deposition in adipocytes by increasing intracellular calcium

BKCa channel participates in insulin-induced lipid deposition in adipocytes by increasing intracellular calcium

  • J Cell Physiol. 2021 Aug;236(8):5818-5831. doi: 10.1002/jcp.30266.
Jie Ren 1 Yuan Cheng 1 Xinxin Wen 1 Ping Liu 1 2 Feng Zhao 1 Fang Xin 1 2 Meili Wang 1 3 Haixia Huang 1 2 3 Wei Wang 1 2
Affiliations

Affiliations

  • 1 Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Beijing, China.
  • 2 Beijing Lab for Cardiovascular Precision Medicine, Beijing, China.
  • 3 Beijing Key Laboratory of Metabolic Disorders Related Cardiovascular Diseases, Capital Medical University, Beijing, China.
Abstract

Storing energy in the form of triglyceride (TG) is one of the basic functions of adipose tissue. Large-conductance calcium-activated potassium channels (BKCa channels) are expressed in adipose tissue and adipocyte-specific BKCa deficiency resists obesity in mice, but the role of BKCa channels in lipid deposition and the underlying mechanisms have not been elucidated. In the present study, we generated BKCa knockout (KO) rats and performed a transcriptome analysis of adipose tissue. We found that the phosphoinositide 3-kinase (PI3K)-protein kinase B (Akt) signaling pathway, which is important for lipid deposition, exhibited the most notable reduction among various signaling pathways in BKCa KO rats compared to wild-type rats. Insulin-induced TG deposition, glucose uptake, and Akt (Ser473) phosphorylation were significantly reduced in cultured adipocytes differentiated from adipose-derived stem cells of BKCa KO rats. Furthermore, we found that the insulin-induced increase of intracellular calcium resulting from extracellular calcium influx was significantly impaired in BKCa KO adipocytes. Finally, Insulin activated BKCa currents through PI3K, which was independent of Akt and intracellular calcium. The results of this study suggested that BKCa channels participate in the Insulin signaling pathway and promote TG deposition by increasing extracellular calcium influx in adipocytes.

Keywords

BKCa channels; adipocyte; insulin; intracellular calcium; triglyceride deposition.

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